猪致病性大肠杆菌耐药性调查复方抗菌制剂筛选及药效研究
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摘要
本研究对全国21个省(市)部分规模化养猪场的812份粪便样品进行了分离、纯化、鉴定,737株分离株被确定为大肠杆菌,对其中的126株进行致病性试验,其中111株为致病性大肠杆菌。采用CLSI(Clinical and Laboratory StandardsInstitute)推荐的K—B(Kirby-Bauer)法,用15种抗菌药物对105株致病性大肠杆菌分离株进行了耐药性检测,检测结果表明:耐药率在80%以上的有四环素(96.2%)、氨苄青霉素(93.3%)、多西环素(88.6%)、恩诺沙星(86.7%)、阿莫西林/棒酸(84.8%)、链霉素(80.0%);耐药率在30%～60%之间的是头孢噻呋钠(51.4%)、氧氟沙星(47.6%)、庆大霉素(40.0%)、新霉素(37.1%);耐药率在30%以下的有氟苯尼考(24.8%)、大观霉素(21%)、安普霉素(17.1%)、多粘菌素B(14.3%)。所检测的105株猪源致病性大肠杆菌对15种抗菌药物产生了不同程度的多重耐药性。
在耐药性调查的基础上,以A药为主药与另外6种抗菌药物进行联合药敏试验,对选择的药物组合进行正交试验及验证试验以确定组方的最佳配比,试验结果表明:A药与6种抗菌药物联合应用均无拮抗作用,其中A药与C药之间表现出较强的协同(相加)作用,当A药、抗菌因子、C药三个组分以2:2:1配比时,复方制剂的抑菌效果最好,其MIC值比A药单用时低4倍,与C药相比,复方制剂对试验菌株MIC值比单用C药时低4—16倍。
对筛选的复方制剂进行了临床药效研究,研究结果表明,使用该复方制剂的中等剂量(即18mg/kg)治疗大肠杆菌引起的腹泻时,治愈率为91.7%,与复方制剂低剂量组、C药对照组、抗菌因子对照组、感染对照组差异显著(0.01＜P＜0.05);试验仔猪的死亡率由正常感染死亡率的30%左右降低为8.3%,与感染对照组差异极显著(P＜0.01)。
In this study, 812 isolation were collected, and 737 isolation of themwere identified as E.coil. Pathogenicity test was done, 111 Pathogenic bacteria were conformed from 126 E. coil. Antimicrobial resistance test was done by K-B method, and 15 kinds of antibiotics were selected for the test. Phenotype Results showed that drug resistance rate were as follows: drug resistance rate higher than 80% were TCY(96.2%)、AMP(93.3%)、DOX(88.6%)、ENR(86.7%)、AMC(84.8%)、STR(80.0%)、drug resistance rate between 60%-30% were :TIO (51.4%)、OFL(47.6%)、GEN(40.0%)、NEO(37.1%); drug resistance rate below 30% were: FLR (24.8%) SPT (21%)、APR (17.1%)、POL (14.3%).
On the basis of drug resistance test, union drug susceptibility test was done, and drug A was selected as main drug, other 6 drugs were selected as adjuvant drug. The best proportion of done by orthogonal experiment. The result showed that drug A has no antagonistic phenomenon with the other 6 drugs. we also found that drug A has strong synergism (add) effect with drug C. Drug A and drug C were show the best efficacy when combined with another adjunct drug, and the best proportion of them is 2:1:2. The MIC value of compound preparation to test organism was four-sixteen times lower than single used drug A or drug C.
The efficacy of the compound preparation was test by clinical experiment , the result indicated that: when medium-dose of compound preparation (18 mg/kg) was used, the cure rate was 91.7%, significantly higher than the low dose group, drug C control group, the control group of anti-bacterial and infection control group's cure rate(0.01< P<0.05). The pigs' mortality rate was reduced from normal mortality rate (about 30%) to 8.3%, significantly lower than infection control group's.
在耐药性调查的基础上,以A药为主药与另外6种抗菌药物进行联合药敏试验,对选择的药物组合进行正交试验及验证试验以确定组方的最佳配比,试验结果表明:A药与6种抗菌药物联合应用均无拮抗作用,其中A药与C药之间表现出较强的协同(相加)作用,当A药、抗菌因子、C药三个组分以2:2:1配比时,复方制剂的抑菌效果最好,其MIC值比A药单用时低4倍,与C药相比,复方制剂对试验菌株MIC值比单用C药时低4—16倍。
对筛选的复方制剂进行了临床药效研究,研究结果表明,使用该复方制剂的中等剂量(即18mg/kg)治疗大肠杆菌引起的腹泻时,治愈率为91.7%,与复方制剂低剂量组、C药对照组、抗菌因子对照组、感染对照组差异显著(0.01＜P＜0.05);试验仔猪的死亡率由正常感染死亡率的30%左右降低为8.3%,与感染对照组差异极显著(P＜0.01)。
In this study, 812 isolation were collected, and 737 isolation of themwere identified as E.coil. Pathogenicity test was done, 111 Pathogenic bacteria were conformed from 126 E. coil. Antimicrobial resistance test was done by K-B method, and 15 kinds of antibiotics were selected for the test. Phenotype Results showed that drug resistance rate were as follows: drug resistance rate higher than 80% were TCY(96.2%)、AMP(93.3%)、DOX(88.6%)、ENR(86.7%)、AMC(84.8%)、STR(80.0%)、drug resistance rate between 60%-30% were :TIO (51.4%)、OFL(47.6%)、GEN(40.0%)、NEO(37.1%); drug resistance rate below 30% were: FLR (24.8%) SPT (21%)、APR (17.1%)、POL (14.3%).
On the basis of drug resistance test, union drug susceptibility test was done, and drug A was selected as main drug, other 6 drugs were selected as adjuvant drug. The best proportion of done by orthogonal experiment. The result showed that drug A has no antagonistic phenomenon with the other 6 drugs. we also found that drug A has strong synergism (add) effect with drug C. Drug A and drug C were show the best efficacy when combined with another adjunct drug, and the best proportion of them is 2:1:2. The MIC value of compound preparation to test organism was four-sixteen times lower than single used drug A or drug C.
The efficacy of the compound preparation was test by clinical experiment , the result indicated that: when medium-dose of compound preparation (18 mg/kg) was used, the cure rate was 91.7%, significantly higher than the low dose group, drug C control group, the control group of anti-bacterial and infection control group's cure rate(0.01< P<0.05). The pigs' mortality rate was reduced from normal mortality rate (about 30%) to 8.3%, significantly lower than infection control group's.
引文
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